Research Article

Photothermal performance of a novel carbon dot and its conjugate with disulfiram for prostate cancer PC3 cell therapy

*Author for correspondence:

Department of Chemistry, Faculty of Chemistry & Chemical Engineering, Graduate University of Advanced Technology, Kerman, 7631818356, Iran

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Leila Montazer

Department of Chemistry, Faculty of Chemistry & Chemical Engineering, Graduate University of Advanced Technology, Kerman, 7631818356, Iran

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Faeze Khakbaz

https://orcid.org/0000-0002-3206-8443

Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, 7616913439, Iran

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Faten Divsar

https://orcid.org/0000-0002-1812-9561

Department of Chemistry, Payame Noor University (PNU), 19395-4697, Tehran, Iran

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Mehdi Yoosefian

https://orcid.org/0000-0003-0096-5083

Department of Chemistry, Faculty of Chemistry & Chemical Engineering, Graduate University of Advanced Technology, Kerman, 7631818356, Iran

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Published Online:15 Nov 2023https://doi.org/10.2217/nnm-2023-0195

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Abstract

Aim: To develop and employ a copper, sulfur, nitrogen–carbon quantum dot (C,S,N-CQD) multifunctional platform for synergistic cancer therapy, combining chemotherapy and photothermal treatment with in vitro cancer cell imaging. Materials & methods: Cu,S,N-CQDs were synthesized hydrothermally, loaded with disulfiram (DSF), and characterized through UV-Vis spectrophotometry, photoluminescence, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy, dynamic light scattering, x-ray diffraction and EDAX. Results: Cu,S,N-CQD exhibited 5.5% absolute fluorescence quantum yield, 46.0% photothermal conversion efficiency and excellent stability. The release of DSF-loaded Cu,S,N-CQD, photothermal performance, and IC₅₀ on PC3 prostate cancer cells, were evaluated. The impact of cellular glutathione on nanocarrier performance was investigated. Conclusion: Cu,S,N-CQD as a photothermal agent and DSF carrier showed synergy (combination index: 0.71) between chemotherapy and photothermal therapy. The nanocarrier simultaneously employed for in vitro cancer cell imaging due to its unique fluorescence properties.

Plain language summary

Nanometer-scale particles can be used to treat and detect cancer in many ways. A type of nanoparticle was designed to attack cancer in two different ways. These nanoparticles – copper, sulfur, nitrogen–carbon quantum dots (C,S,N–CQDs) – were designed to both deliver a chemotherapy drug to cancer cells and act as a photothermal agent. This means that when light of a particular energy is shone on these particles, they heat up and can kill cancer cells. These C,S,N–CQDs loaded with the chemotherapy drug disulfiram were then tested on the prostate cancer cell line PC3. When a laser was shone on these particles and they became excited, they reduced cancer cell viability both by releasing the drug and heating up and killing the surrounding cells. These Cu,S,N-CQDs are also fluorescent, meaning they can be used to image cancer cells in tests like these.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Qian F, Li X, Tang L, Lai SK, Lu C, Lau SP. Potassium doping: tuning the optical properties of graphene quantum dots. AIP Adv. 6(7), 075116 (2016).
Google Scholar
2. Qian Z, Ma J, Shan X et al. Surface functionalization of graphene quantum dots with small organic molecules from photoluminescence modulation to bioimaging applications: an experimental and theoretical investigation. RSC Adv. 3(34), 14571–14579 (2013).
CASGoogle Scholar
3. Peynshaert K, Soenen SJ, Manshian BB et al. Coating of quantum dots strongly defines their effect on lysosomal health and autophagy. Acta Biomater. 48, 195–205 (2017).
Medline CASGoogle Scholar
4. Dirheimer L, Pons T, Marchal F, Bezdetnaya L. Quantum dots mediated imaging and phototherapy in cancer spheroid models: state of the art and perspectives. Pharmaceutics 14(10), 2136 (2022).
Medline CASGoogle Scholar
5. Khakbaz F, Mirzaei M, Mahani M. Lecithin sensitized thermo-sensitive niosome using NIR-carbon dots for breast cancer combined chemo-photothermal therapy. J. Photochem. Photobiol. A: Chem. 434, 114236 (2023). •• Describes loading niosomes with carbon quantum dots (CQDs) and drug for combination therapy.
CASGoogle Scholar
6. Xie Z, Fan T, An J et al. Emerging combination strategies with phototherapy in cancer nanomedicine. Chem. Soc. Rev. 49(22), 8065–8087 (2020). • Review on combinatorial strategies of phototherapy with other therapeutic methods, including chemotherapy, immunotherapy, gene therapy and radiotherapy.
Medline CASGoogle Scholar
7. Wang J, Sun J, Wang Y et al. Gold nanoframeworks with mesopores for Raman-photoacoustic imaging and photo-chemo tumor therapy in the second near-infrared biowindow. Adv. Funct. Mater. 30(9), 1908825 (2020).
Medline CASGoogle Scholar
8. Lin K, Cao Y, Zheng D et al. Facile phase transfer of hydrophobic Fe₃O₄@Cu₂-xS nanoparticles by red blood cell membrane for MRI and phototherapy in the second near-infrared window. J. Mater. Chem. B 8(6), 1202–1211 (2020).
Medline CASGoogle Scholar
9. Mahani M, Khakbaz F, Ju H. Hairpin oligosensor using SiQDs: förster resonance energy transfer study and application for miRNA-21 detection. Anal. Bioanal. Chem. 414(7), 2505–2512 (2022).
Medline CASGoogle Scholar
10. Mahani M, Alimohamadi F, Torkzadeh-Mahani M et al. LSPR biosensing for the early-stage prostate cancer detection using hydrogen bonds between PSA and antibody: molecular dynamic and experimental study. J. Mol. Liq. 324, 114736 (2021).
CASGoogle Scholar
11. Salahvarzi A, Mahani M, Torkzadeh-Mahani M, Alizadeh R. Localized surface plasmon resonance based gold nanobiosensor: determination of thyroid stimulating hormone. Anal. Biochem. 516, 1–5 (2017).
Medline CASGoogle Scholar
12. Faridli Z, Mahani M, Torkzadeh-Mahani M, Fasihi J. Development of a localized surface plasmon resonance-based gold nanobiosensor for the determination of prolactin hormone in human serum. Anal. Biochem. 495, 32–36 (2016).
Medline CASGoogle Scholar
13. Jiang K, Wang Y, Gao X, Cai C, Lin H. Facile, quick, and gram-scale synthesis of ultralong-lifetime room-temperature-phosphorescent carbon dots by microwave irradiation. Angew. Chem. Int. Ed. 57(21), 6216–6220 (2018).
Medline CASGoogle Scholar
14. Liu ML, Chen BB, Li CM, Huang CZ. Carbon dots: synthesis, formation mechanism, fluorescence origin and sensing applications. Green Chem. 21(3), 449–471 (2019).
CASGoogle Scholar
15. Zhang Z, Yi G, Li P et al. A minireview on doped carbon dots for photocatalytic and electrocatalytic applications. Nanoscale 12(26), 13899–13906 (2020).
Medline CASGoogle Scholar
16. Meena R, Singh R, Marappan G et al. Fluorescent carbon dots driven from ayurvedic medicinal plants for cancer cell imaging and phototherapy. Heliyon 5(9), e02483 (2019).
Medline CASGoogle Scholar
17. Sun S, Zhang L, Jiang K, Wu A, Lin H. Toward high-efficient red emissive carbon dots: facile preparation, unique properties, and applications as multifunctional theranostic agents. Chem. Mater. 28(23), 8659–8668 (2016).
CASGoogle Scholar
18. Liu C, Zhang P, Tian F, Li W, Li F, Liu W. One-step synthesis of surface passivated carbon nanodots by microwave assisted pyrolysis for enhanced multicolor photoluminescence and bioimaging. J. Mater. Chem. 21(35), 13163–13167 (2011).
CASGoogle Scholar
19. Liu C, Zhang P, Zhai X et al. Nano-carrier for gene delivery and bioimaging based on carbon dots with PEI-passivation enhanced fluorescence. Biomaterials 33(13), 3604–3613 (2012).
Medline CASGoogle Scholar
20. Jiang Q, Liu L, Li Q et al. NIR-laser-triggered gadolinium-doped carbon dots for magnetic resonance imaging, drug delivery and combined photothermal chemotherapy for triple negative breast cancer. J. Nanobiotechnol. 19(1), 1–15 (2021).
MedlineGoogle Scholar
21. Nichols F, Lu JE, Mercado R et al. Antibacterial activity of nitrogen-doped carbon dots enhanced by atomic dispersion of copper. Langmuir 36(39), 11629–11636 (2020).
Medline CASGoogle Scholar
22. Sun S, Chen Q, Tang Z et al. Tumor microenvironment stimuli-responsive fluorescence imaging and synergistic cancer therapy by carbon-dot-Cu²⁺ nanoassemblies. Angew. Chem. 132(47), 21227–21234 (2020). •• Cu/CC nanoparticles act as photothermal therapy (PTT), photodynamic therapy (PDT) and thermally amplified chemodynamic therapy agent.
Google Scholar
23. Bao Y-W, Hua X-W, Li Y-H, Jia H-R, Wu F-G. Hyperthemia-promoted cytosolic and nuclear delivery of copper/carbon quantum dot-crosslinked nanosheets: multimodal imaging-guided photothermal cancer therapy. ACS Appl. Mater. Interfaces 10(2), 1544–1555 (2018).
Medline CASGoogle Scholar
24. Permatasari FA, Fukazawa H, Ogi T, Iskandar F, Okuyama K. Design of pyrrolic-N-rich carbon dots with absorption in the first near-infrared window for photothermal therapy. ACS Appl. Nano Mater. 1(5), 2368–2375 (2018).
CASGoogle Scholar
25. Ge J, Jia Q, Liu W et al. Red-emissive carbon dots for fluorescent, photoacoustic, and thermal theranostics in living mice. Adv. Mater. 27(28), 4169–4177 (2015). • Strong photoacoustic response and photothermal effect using red-emissive CQDs.
Medline CASGoogle Scholar
26. Bao X, Yuan Y, Chen J et al. In vivo theranostics with near-infrared-emitting carbon dots-highly efficient photothermal therapy based on passive targeting after intravenous administration. Light Sci. Appl. 7(1), 1–11 (2018).
MedlineGoogle Scholar
27. Geng B, Yang D, Pan D et al. NIR-responsive carbon dots for efficient photothermal cancer therapy at low power densities. Carbon 134, 153–162 (2018).
CASGoogle Scholar
28. Mahani M, Bahmanpouri M, Khakbaz F, Divsar F. Doxorubicin-loaded polymeric micelles decorated with nitrogen-doped carbon dots for targeted breast cancer therapy. J. Drug Deliv. Sci. Technol. 79, 104055 (2023). • Describes the application of polymeric micelles for cancer therapy.
CASGoogle Scholar
29. Mahani M, Faghihi-Fard M, Divsar F, Torkzadeh-Mahani M, Khakbaz F. Ultrasensitive FRET-based aptasensor for interleukin-6 as a biomarker for COVID-19 progression using nitrogen-doped carbon quantum dots and gold nanoparticles. Microchim. Acta 189(12), 1–8 (2022).
Google Scholar
30. Mahani M, Taheri M, Divsar F, Khakbaz F, Nomani A, Ju H. Label-free triplex DNA-based biosensing of transcription factor using fluorescence resonance energy transfer between N-doped carbon dot and gold nanoparticle. Anal. Chim. Acta 1181, 338919 (2021).
Medline CASGoogle Scholar
31. Saljoughi H, Khakbaz F, Mahani M. Synthesis of folic acid conjugated photoluminescent carbon quantum dots with ultrahigh quantum yield for targeted cancer cell fluorescence imaging. Photodiagnosis Photodyn. Ther. 30, 101687 (2020).
Medline CASGoogle Scholar
32. Mahani M, Mousapour Z, Divsar F, Nomani A, Ju H. A carbon dot and molecular beacon based fluorometric sensor for the cancer marker microRNA-21. Microchim. Acta 186(3), 1–8 (2019).
CASGoogle Scholar
33. Khakbaz F, Mahani M. Micro-RNA detection based on fluorescence resonance energy transfer of DNA-carbon quantum dots probes. Anal. Biochem. 523, 32–38 (2017).
Medline CASGoogle Scholar
34. Rahimi M, Mahani M, Hassani Z. Carbon quantum dots fluorescence quenching for potassium optode construction. Luminescence 34(4), 402–406 (2019).
Medline CASGoogle Scholar
35. Mahani M, Karimi-Mazidi P, Khakbaz F, Torkzadeh-Mahani M. Carbon quantum dots-Annexin V probe: photoinduced electron transfer mechanism, phosphatidylserine detection, and apoptotic cell imaging. Microchim. Acta 189(2), 69 (2022).
Medline CASGoogle Scholar
36. Mahani M, Mahmoudi F, Fassihi J, Hasani Z, Divsar F. Carbon dots-embedded N-acetylneuraminic acid and glucuronic acid-imprinted polymers for targeting and imaging of cancer cells. Microchim. Acta 188(7), 224 (2021).
Medline CASGoogle Scholar
37. Hossainzadeh S, Ranji N, Naderi Sohi A, Najafi F. Silibinin encapsulation in polymersome: a promising anticancer nanoparticle for inducing apoptosis and decreasing the expression level of miR-125b/miR-182 in human breast cancer cells. J. Cell. Physiol. 234(12), 22285–22298 (2019).
Medline CASGoogle Scholar
38. Mahani M, Pourrahmani-Sarbanani M, Yoosefian M, Divsar F, Mousavi SM, Nomani A. Doxorubicin delivery to breast cancer cells with transferrin-targeted carbon quantum dots: an in vitro and in silico study. J. Drug Deliv. Sci. Technol. 62, 102342 (2021).
CASGoogle Scholar
39. Hu Y, Yang J, Tian J, Yu J-S. How do nitrogen-doped carbon dots generate from molecular precursors? An investigation of the formation mechanism and a solution-based large-scale synthesis. J. Mater. Chem. B 3(27), 5608–5614 (2015). • Describes the formation mechanism of CQDs from precursors.
Medline CASGoogle Scholar
40. Roper DK, Ahn W, Hoepfner M. Microscale heat transfer transduced by surface plasmon resonant gold nanoparticles. J. Phys. Chem. C 111(9), 3636–3641 (2007).
CASGoogle Scholar
41. Tian Q, Jiang F, Zou R et al. Hydrophilic Cu9S5 nanocrystals: a photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo. ACS Nano 5(12), 9761–9771 (2011).
Medline CASGoogle Scholar
42. Lewis DJ, Deshmukh P, Tedstone AA, Tuna F, O'Brien P. On the interaction of copper (II) with disulfiram. Chem. Comm. 50(87), 13334–13337 (2014).
Medline CASGoogle Scholar
43. Zhang X, Ren X, Tang J et al. Hyaluronic acid reduction-sensitive polymeric micelles achieving co-delivery of tumor-targeting paclitaxel/apatinib effectively reverse cancer multidrug resistance. Drug Deliv. 27(1), 825–835 (2020).
Medline CASGoogle Scholar
44. Lei W, Sun C, Jiang T et al. Polydopamine-coated mesoporous silica nanoparticles for multi-responsive drug delivery and combined chemo-photothermal therapy. Mater. Sci. Eng. C 105, 110103 (2019).
Medline CASGoogle Scholar
45. Greco WR. The search for synergy: a critical review from a response surface perspective. Pharmacol. Rev. 47, 331–385 (1995).
Medline CASGoogle Scholar
46. Saito G, Swanson JA, Lee K-D. Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv. Drug Deliv. Rev. 55(2), 199–215 (2003). •• Review on recent discoveries on disulfide reductions.
Medline CASGoogle Scholar
47. Ock K, Jeon WI, Ganbold EO et al. Real-time monitoring of glutathione-triggered thiopurine anticancer drug release in live cells investigated by surface-enhanced Raman scattering. Anal. Chem. 84(5), 2172–2178 (2012).
Medline CASGoogle Scholar
48. Zhao X, Xi Y, Zhang Y et al. Redox-sensitive gelatin/silica-aptamer nanogels for targeted siRNA delivery. Nanoscale Res. Lett. 14(1), 1–9 (2019).
MedlineGoogle Scholar
49. Cen D, Gonzalez RI, Buckmeier JA, Kahlon RS, Tohidian NB, Meyskens FL Jr. Disulfiram induces apoptosis in human melanoma cells: a redox-related process. Mol. Cancer Ther. 1(3), 197–204 (2002).
Medline CASGoogle Scholar
50. Ohno Y, Hirota K, Kawanishi T, Takanaka A. Loss of viability after disulfiram treatment without preceding depletion of intracellular GSH. J. Toxicol. Sci. 15(2), 63–73 (1990).
Medline CASGoogle Scholar
51. Chen M, Huang Z, Xia M et al. Glutathione-responsive copper-disulfiram nanoparticles for enhanced tumor chemotherapy. J. Control. Rel. 341, 351–363 (2022). •• Discusses the transformation from low toxicity to high toxicity for disulfiram-based chemotherapy.
Medline CASGoogle Scholar
52. Tawari PE, Wang Z, Najlah M et al. The cytotoxic mechanisms of disulfiram and copper(ii) in cancer cells. Toxicol. Res. (Camb.) 4(6), 1439–1442 (2015).
Medline CASGoogle Scholar

Vol. 18, No. 24

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History

Received 23 July 2023

Accepted 22 September 2023

Published online 15 November 2023

Published in print October 2023

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To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0195

Financial disclosure

This work was supported by Graduate University of Advanced Technology, Kerman, Iran (grant no. 00/2704). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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No writing assistance was utilized in the production of this manuscript.

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